蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

doi:10.16352/j.issn.1001-6325.2022.07.1026

基础医学与临床 ›› 2022, Vol. 42 ›› Issue (7): 1026-1030.doi: 10.16352/j.issn.1001-6325.2022.07.1026

蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

胡欣俊, 余东林, 范宏, 韩改净, 薛征^*, 吕湘^*

中国医学科学院基础医学研究所北京协和医学院基础学院病理生理学系医学分子生物学国家重点实验室,北京 100005

收稿日期:2022-03-28 修回日期:2022-04-27 出版日期:2022-07-05 发布日期:2022-06-29
通讯作者: * lvxiang@pumc.edu.cn; xuezheng@ibms.pumc.edu.cn
基金资助:
国家自然科学基金(82170120)

Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells

HU Xin-jun, YU Dong-lin, FAN Hong, HAN Gai-jing, XUE Zheng^*, LYU Xiang^*

State Key Laboratory of Medical Molecular Biology, Department of Pathophysiology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005

Received:2022-03-28 Revised:2022-04-27 Online:2022-07-05 Published:2022-06-29
Contact: * lvxiang@pumc.edu.cn; xuezheng@ibms.pumc.edu.cn

摘要/Abstract

摘要： 目的探索在小鼠胎肝来源红系细胞中蛋白酪氨酸磷酸酶4A3(PTP4A3)在红系终末分化和脱核中的作用及分子机制。方法 RT-qPCR检测Ptp4a3在终末分化过程中的表达情况。利用短发夹RNA(shRNA)干扰技术在小鼠胎肝诱导红系分化体系中敲低Ptp4a3的表达,流式细胞分选GFP阳性细胞后RT-qPCR验证其敲低效率,流式细胞测量术分析检测Ptp4a3敲低后对红系分化和脱核的影响。RNA表达谱测序并分析在红系细胞终末分化过程中Ptp4a3敲低影响的通路和基因。结果 PTP4A3在红系细胞终末分化过程中表达水平逐渐升高。在小鼠胎肝来源红系细胞中成功敲低Ptp4a3的表达,流式细胞测量术检测发现敲低Ptp4a3可显著降低红系细胞脱核率(P＜0.05)。表达谱分析发现敲低Ptp4a3影响红系终末分化过程中细胞周期相关基因表达。结论 PTP4A3在红系细胞终末分化晚期高表达,并参与调控细胞脱核过程。

关键词: 蛋白酪氨酸磷酸酶4A3, 红系终末分化, 红系脱核, 细胞周期

Abstract: Objective To investigate the expression and function of protein tyrosine phosphatase 4A3(PTP4A3) in terminal erythroid differentiation and underlying molecular mechanism. Methods RT-qPCR was used to detect the expression of Ptp4a3 during terminal differentiation. Knockdown of Ptp4a3 expression in mouse fetal liver induced erythroid differentiation system by short hairpin RNA(shRNA) interference, the knockdown efficiency was verified by RT-qPCR after GFP positive cells were sorted by flow cytometry, and the effect of Ptp4a3 knockdown on erythroid differentiation and enucleation was detected by flow cytometry. Transcriptional profiling was performed to explore the potential downstream pathways of Ptp4a3. Results Ptp4a3 was among the top 100 ranked expressing genes during mouse terminal erythroid differentiation, and its expression gradually increased following the differentiation process. In mouse fetal liver-derived erythroid cells, Ptp4a3 was successfully knocked down by shRNA interference. Flow cytometry analysis showed that Ptp4a3 knockdown significantly decreased the proportion of enucleated erythrocytes(P＜0.05). Transcriptome analysis revealed that Ptp4a3 knockdown resulted in upregulation of cell cycle-related genes. Conclusions PTP4A3 is highly expressed in late stage of terminal erythroid differentiation. Knockdown Ptp4a3 significantly reduces enucleation erythroid of cells.

Key words: protein tyrosine phosphatase 4A3, terminal erythroid differentiation, erythroid enucleation, cell cycle

中图分类号:

胡欣俊, 余东林, 范宏, 韩改净, 薛征, 吕湘. 蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核[J]. 基础医学与临床, 2022, 42(7): 1026-1030.

HU Xin-jun, YU Dong-lin, FAN Hong, HAN Gai-jing, XUE Zheng, LYU Xiang. Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells[J]. Basic & Clinical Medicine, 2022, 42(7): 1026-1030.

0
/ / 推荐

导出引用管理器 EndNote|Reference Manager|ProCite|BibTeX|RefWorks

链接本文: http://journal11.magtechjournal.com/Jwk_jcyxylc/CN/10.16352/j.issn.1001-6325.2022.07.1026

http://journal11.magtechjournal.com/Jwk_jcyxylc/CN/Y2022/V42/I7/1026

参考文献 12

[1]	Pu Y, Sun F, Sun R, et al.PTP4A3, a novel target gene of HIF-1alpha, participates in benzene-induced cell proliferation inhibition and apoptosis through PI3K/AKT pathway[J].Int J Environ Res Public Health,2020, 17:901.doi:10.3390/ijerph17030910.
[2]	Duciel L, Anezo O, Mandal K, et al.Protein tyrosine phosphatase 4A3 (PTP4A3/PRL-3) promotes the aggressiveness of human uveal melanoma through dephosphorylation of CRMP2[J].Sci Rep,2019, 9: 2990.doi:10.1038/s41598-019-39643-5.
[3]	Basak S, Jacobs SB, Krieg AJ, et al.The metastasis-associated gene Prl-3 is a p53 target involved in cell-cycle regulation[J].Mol Cell,2008, 30: 303-314.
[4]	Cromer MK, Camarena J, Martin RM, et al.Gene replacement of α-globin with β-globin restores hemoglobin balance in β-thalassemia-derived hematopoietic stem and progenitor cells[J].Nat Med,2021, 27: 677-687.
[5]	Bekri S, May A, Cotter P D, et al.A promoter mutation in the erythroid-specific 5-aminolevulinate synthase (ALAS2) gene causes X-linked sideroblastic anemia[J].Blood,2003, 102: 698-704.
[6]	Ulirsch JC, Nandakumar SK, Wang L, et al.Systematic functional dissection of common genetic variation affecting red blood cell traits[J].Cell,2016, 165: 1530-1545.
[7]	Alvarez-Dominguez JR, Zhang X, Hu W.Widespread and dynamic translational control of red blood cell development[J].Blood,2017, 129: 619-629.
[8]	Wang J, Ramirez T, Ji P, et al.Mammalian erythroblast enucleation requires PI3K-dependent cell polarization[J].J Cell Sci,2012, 125(Pt 2): 340-349.
[9]	Lu Z, Huang L, Li Y, et al.Fine-tuning of cholesterol homeostasis controls erythroid differentiation[J].Adv Sci(Weinh),2022, 9: e2102669.doi:10.1002/advs.202102669.
[10]	Hattangadi SM, Martinez-Morilla S, Patterson HC, et al.Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation[J].Blood,2014, 124: 1931-1940.
[11]	Kinross KM, Clark AJ, Iazzolino RM, et al.E2f4 regulates fetal erythropoiesis through the promotion of cellular proliferation[J].Blood,2006, 108: 886-895.
[12]	Sankaran VG, Ludwig LS, Sicinska E, et al.Cyclin D3 coordinates the cell cycle during differentiation to regulate erythrocyte size and number[J].Genes Dev,2012, 26: 2075-2087.

[1]	余东林, 杨希, 阴佳滢, 刘雪会, 吕湘. 核转录因子NFYB和NFYC促进红系终末分化[J]. 基础医学与临床, 2022, 42(6): 920-926.
[2]	李阳芳, 胡慧敏. PTTG和p21作为无功能垂体瘤放射治疗预后的分子标志物[J]. 基础医学与临床, 2021, 41(9): 1253-1259.
[3]	蔡波, 邢娟娟, 胡蓉, 任欣, 王榕, 吴恬宁, 郭菲, 陈少卿. 组蛋白H3K27甲基化对人高分化鼻咽癌细胞系CNE-1增殖的抑制效应[J]. 基础医学与临床, 2020, 40(12): 1613-1618.
[4]	陈连香曹丽霞. miR-150通过调节c-Myb抑制人慢性髓系白血病细胞系K562增殖[J]. 基础医学与临床, 2019, 39(9): 1259-1264.
[5]	张战锋谢在春庞志宇陈久凯周迎春. NF2基因在丙肝病毒非结构蛋白4B调节细胞周期中的作用[J]. 基础医学与临床, 2019, 39(9): 1289-1293.
[6]	周琳喻修为陶凯杨诚诚刘胜春. luminal A 型乳腺癌组织中长链非编码RNA ENST00000460164的表达及对细胞周期的影响[J]. 基础医学与临床, 2017, 37(7): 1037-1041.
[7]	鹿文葆刘明明修瑞娟. MCPIP1诱导乳腺癌MDA-MB-231细胞细胞周期停滞[J]. 基础医学与临床, 2017, 37(5): 608-613.
[8]	张新然强兆艳庄昊韩风李咏梅. GDF15表达下调促进人胶质母细胞瘤细胞系U87MG增殖[J]. 基础医学与临床, 2017, 37(11): 1557-1561.
[9]	唐振东慈雅丽杨洋许彩民. 亚硒酸钠诱导结直肠癌SW480细胞系凋亡[J]. 基础医学与临床, 2016, 36(12): 1630-1635.
[10]	谭正兰何晓燕陈卉刘姗余朝文邹琳. miR-221促进神经母细胞瘤SH-SY5Y细胞N-MYC表达和细胞增殖[J]. 基础医学与临床, 2016, 36(10): 1329-1334.
[11]	王改平陈莎莎李晓芳杨婧赵卫明常翠芳徐存拴. 人胰岛素抑制大鼠肝细胞系BRL-3A凋亡且促增殖[J]. 基础医学与临床, 2015, 35(10): 1320-1324.
[12]	何政吴慧万荣华郑军. siRNA沉默CD55基因对胰腺癌BxPC-3细胞增殖的影响[J]. 基础医学与临床, 2014, 34(7): 974-978.
[13]	李博王元刚李娟汤海峰程光. 白头翁皂苷—D诱导U87MG细胞凋亡[J]. 基础医学与临床, 2014, 34(5): 654-660.
[14]	张秀梅张霞肖建英. RNA干扰Glut1表达对MCF-7细胞增殖的影响[J]. 基础医学与临床, 2014, 34(4): 546-547.
[15]	郭利华邵晓娜朱华陀陈文果李岚虞朝辉陈李华. 1α,25(OH) 2D3阻滞细胞周期抑制胃癌细胞株增殖[J]. 基础医学与临床, 2014, 34(2): 201-205.

蛋白酪氨酸磷酸酶4A3(PTP4A3)促进小鼠胎肝来源红系细胞脱核

Protein tyrosine phosphatase 4A3(PTP4A3) promotes enucleation in mouse fetal liver-derived erythroid cells

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献 12

相关文章 15

编辑推荐

Metrics

本文评价